| Eligibility |
Inclusion Criteria:
- Patient has a diagnosis of schizophrenia or schizoaffective disorder according to the
Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria.
- A patient is considered operationally stable if the patient has a low to moderate
positive symptoms score and moderate negative symptom score on the Positive and
Negative Syndrome Scale (PANSS): No more than moderate rating on more than 2 PANSS
items P1, P2, P3, P5, P6 (positive symptom section); No more than moderate severity
rating for the negative items, N1, N2, N3, N4, N5, N6, N7 (negative symptom section);
total PANSS score no more than 80.
- Patient must be in ongoing maintenance antipsychotic therapy other than clozapine
(oral or depot), on a stable (= 25% change in dose) medication treatment regimen
(approved oral or depot formulations of risperidone, quetiapine, olanzapine,
ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone) for = 2 months
for oral formulations or = 3 months for depot formulations prior to screening,
including concomitant psychotropic medications, such as, trazodone and zolpidem for
sleep.
- Patient has a body mass index (BMI) range of 18.5 to 40.0 kg/m2, inclusive, and weighs
at least 50 kg at screening.
- Female patient must be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses) prior to
screening, or
- Documented surgically sterile (at least 1 month prior to screening defined as
hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy)
- Female patient must not donate ova starting at screening and throughout the study
period, and for 28 days after the final study drug administration.
- Male patient and their female spouse/partners who are of childbearing potential must
be using 2 forms of highly effective birth control† (1 of which must be a barrier
method‡) starting at screening and continue throughout the study period and for 90
days after the final study drug administration.
†Highly effective forms of birth control include:
- Consistent and correct usage of established oral contraception
- Injected or implanted hormonal methods of contraception
- Established intrauterine device or intrauterine system
- Bilateral tubal ligation
- Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk
associated with the study treatments and complies with the preferred and usual
lifestyle of the patient.
‡Barrier methods of birth control include:
- Condom with spermicidal foam/gel/film/cream/suppository
- Occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository
- Male patient must not donate sperm starting at screening and throughout the study
period and for 90 days after the final study drug administration.
- Patient agrees not to participate in another interventional study while participating
in the present study, defined as signing the informed consent form until the end of
study visit (ESV).
- Patient has a negative urine drug screen for drugs of abuse at screening and check in.
Exclusion Criteria:
- Female patient who has been pregnant within 6 months prior to screening assessment or
breastfeeding within 3 months prior to screening.
- Patient has a known or suspected hypersensitivity to ASP4345 or any components of the
formulation used.
- Patient has had previous exposure with ASP4345.
- Patient has a history of suicide attempt or suicidal behavior within 2 years prior to
screening. Any suicidal ideation that meets criteria at a level of 4 or 5 by using
C-SSRS within the last 3 months or who is at significant risk to commit suicide at
screening or at admission to the clinical unit (day 2) will be excluded.
- Patient has any clinically significant liver chemistry test result aspartate
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP),
gamma glutamyl transferase, total bilirubin (TBL) or a result > than 1.5 times above
the ULN at screening or at admission to the clinical unit (day 2). In such a case, the
assessment may be repeated once.
- Patient has any history of allergic conditions deemed clinically significant.
- Patient has any history or evidence of any clinically significant cardiovascular,
gastrointestinal endocrinologic, hematologic, hepatic, immunologic, metabolic,
urologic, pulmonary, neurologic, dermatologic, psychiatric (other than schizophrenia
or schizoaffective disorder), renal and/or other major disease or malignancy. Patient
has any condition, which, makes the patient unsuitable for clinical study
participation.
- Patient has been diagnosed with moderate or severe tardive dyskinesia, bipolar
disorder, major depressive disorder, personality disorders, neuroleptic malignancy
syndrome or anxiety disorder.
- Patient has/had febrile illness or symptomatic, viral, bacterial (including upper
respiratory infection) or fungal (noncutaneous) infection within 1 week prior to
admission to the clinical unit (day 2).
- Patient has any clinically significant abnormality at screening or at admission to the
clinical unit (day 2).
- Patient has a mean pulse < 40 or > 100 bpm; mean systolic blood pressure (SBP) > 160
mmHg; mean diastolic blood pressure (DBP) > 90 mmHg (vital signs measurements taken in
triplicate after patient has been resting in supine position for 5 minutes; pulse will
be measured automatically) at screening or at admission to the clinical unit (day 2).
If the mean blood pressure exceeds the limits above, 1 additional triplicate can be
taken on day 2.
- Patient has a mean QTcF > 440 msec (for male patients) and > 460 msec (for female
patients) at screening or at admission to the clinical unit (day 2). If the mean QTcF
exceeds the limits above, 1 additional triplicate ECG can be taken on day 2.
- Patient uses any prescribed or nonprescribed drugs (including vitamins, natural and
herbal remedies, e.g., Valerian) in the 2 weeks prior to study drug administration,
except for:
1. Approved antipsychotics (risperidone, quetiapine, olanzapine, ziprasidone,
brexpiprazole, aripiprazole, paliperidone or lurasidone), or
2. Approved intermittent use of trazodone or zolpidem (no less than 12 hours prior
to dosing), or
3. Approved use of concomitant medication for the treatment of hypertension,
hyperlipidemia or diabetes mellitus, or
4. Occasional use of acetaminophen (up to 2 g/day).
- Patient has a history of consuming more than 14 units of alcoholic beverages per week
within 6 months prior to screening or has a history of alcoholism or
drug/chemical/substance abuse within past 2 years prior to screening (Note: 1 unit =
12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the patient
tests positive for alcohol or drugs of abuse (amphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine and opiates) at screening or at admission to
the clinical unit (day 2). A patient with a positive result for benzodiazepines may be
included in this clinical study, if the result can be explained by the use of
permitted concomitant medication.
- Patient has used any strong CYP3A inhibitors (e.g., but not limited to: boceprevir,
clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole,
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir,
saquinavir, telaprevir, telithromycin, voriconazole) and/or has consumed grapefruit,
grapefruit containing products, Seville orange or Seville orange containing products
within 72 hours prior to admission to the clinical unit (day 2).
- Patient has used any strong or moderate CYP2D6 inhibitors (e.g., but not limited to:
bupropion, fluoxetine, paroxetine, quinidine, cinacalcet, duloxetine, terbinafine)
within 72 hours prior to admission to the clinical unit (day 2).
- Patient regularly uses any inducer of metabolism (e.g., but not limited to:
barbiturates, rifampin, St. John's Wort) in the 1 month prior to admission to the
clinical unit (day 2).
- Patient has used any drugs of abuse within 3 months prior to admission to the clinical
unit (day 2).
- Patient has had significant blood loss, donated 1 unit (450 mL) of blood or more, or
received a transfusion of any blood or blood products within 60 days or donated plasma
within 7 days prior to admission to the clinical unit (day 2).
- Patient has a positive serology test for hepatitis B surface antigen (HBsAg),
hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM]), hepatitis C virus (HCV)
antibodies, or human immunodeficiency virus (HIV) antibodies type 1 or 2 at screening.
- Patient has participated in any clinical study or has been treated with any
investigational drugs within 28 days or 5 half lives whichever is longer, prior to
screening.
- Patient is an employee of the Astellas Group or Contract Research Organization (CRO)
involved in the clinical study.
- Patient who has had electroconvulsive therapy within the 6 months prior to screening.
- Patient has a history of seizures or of a condition with risk of seizures; as an
exception, a history of 1 febrile seizure in childhood will not exclude a patient.
- Patient has a history of head injury with clinically significant sequelae.
- Patient experienced an acute exacerbation of schizophrenia requiring hospitalization
within the last 3 months.
- Patient experienced an acute exacerbation of schizophrenia requiring increase in
antipsychotic medication (with reference to drug or dose) within the last 4 weeks.
- Patient has hearing loss, is unable to detect 1000 Hz tones presented at 40 dB.
- Patient has a hairstyle that would interfere with electroencephalogram (EEG) recording
quality.
- Patient has a history of spine surgery (with intact dura mater) in the past year
and/or a history of brain and/or spinal cord injury.
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